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Reduction of sensory and metabotropic glutamate receptor responses in the thalamus by the novel metabotropic glutamate receptor-1-selective antagonist S-2-methyl-4-carboxy-phenylglycine
- Source :
- Neuroscience. 85:655-658
- Publication Year :
- 1998
- Publisher :
- Elsevier BV, 1998.
-
Abstract
- Previous work has shown that responses of thalamic neurons in vivo to the metabotropic glutamate receptor agonists 1S,3R-aminocyclopentane-1,3-dicarboxylate and S-3,5-dihydroxyphenylglycine can be reduced by a variety of phenylglycine antagonists. Responses of thalamic neurons to noxious thermal somatosensory stimuli were reduced in parallel by these antagonists, indicating that these responses are mediated by Group I metabotropic glutamate receptors (i.e. metabotropic glutamate receptor-1 and/or metabotropic glutamate receptor-5), which are known to be linked to phosphoinositol phosphate hydrolysis. The recent development of S-2-methyl-4-carboxyphenylglycine as an antagonist which is highly selective for metabotropic glutamate receptor-1 compared to metabotropic glutamate receptor-5 on human receptors expressed in AV-12 cells, now offers the possibility of discriminating between these two receptor subtypes in order to distinguish which is involved in thalamic responses. We have made recordings from single somatosensory neurons in the thalamus of the rat, and find that S-2-methyl-4-carboxy-phenylglycine is able to reduce responses of neurons to 1S,3R-aminocyclopentane-1,3-dicarboxylate, S-3,5-dihydroxyphenylglycine, and noxious stimuli without significant effect on responses to either N-methyl-D-aspartate or (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. These results suggest that excitatory responses of thalamic neurons to 1S,3R-aminocyclopentane-1,3-dicarboxylate and S-3,5-dihydroxyphenylglycine may be mediated by metabotropic glutamate receptor-1. Furthermore, the reduction of nociceptive responses by S-2-methyl-4-carboxy-phenylglycine indicates that metabotropic glutamate receptor-1 is involved in thalamic nociceptive processing and that such antagonists may have analgesic properties.
- Subjects :
- Male
N-Methylaspartate
Glycine
Naphthols
Biology
Receptors, Metabotropic Glutamate
Benzoates
Thalamus
Excitatory Amino Acid Agonists
Animals
Cycloleucine
Neurons, Afferent
Rats, Wistar
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Metabotropic glutamate receptor 8
Metabotropic glutamate receptor 5
General Neuroscience
Metabotropic glutamate receptor 4
Metabotropic glutamate receptor 7
Metabotropic glutamate receptor 6
Rats
Electrophysiology
Neuroprotective Agents
Propylene Glycols
Metabotropic glutamate receptor 1
Metabotropic glutamate receptor 3
Metabotropic glutamate receptor 2
Excitatory Amino Acid Antagonists
Neuroscience
Subjects
Details
- ISSN :
- 03064522
- Volume :
- 85
- Database :
- OpenAIRE
- Journal :
- Neuroscience
- Accession number :
- edsair.doi.dedup.....f0d3f2283b88a8992dd08e498f5d217c